Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4658 | 14197;14198;14199 | chr2:178739261;178739260;178739259 | chr2:179603988;179603987;179603986 |
| N2AB | 4341 | 13246;13247;13248 | chr2:178739261;178739260;178739259 | chr2:179603988;179603987;179603986 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4295 | 13108;13109;13110 | chr2:178739261;178739260;178739259 | chr2:179603988;179603987;179603986 |
| Novex-1 | 4420 | 13483;13484;13485 | chr2:178739261;178739260;178739259 | chr2:179603988;179603987;179603986 |
| Novex-2 | 4487 | 13684;13685;13686 | chr2:178739261;178739260;178739259 | chr2:179603988;179603987;179603986 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs758799742  |
0.12 | 0.007 | N | 0.321 | 0.126 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| T/I | rs758799742 |
0.12 | 0.007 | N | 0.321 | 0.126 | None | gnomAD-4.0.0 | 5.49212E-06 | None | None | None | None | N | None | 0 | 2.24507E-05 | None | 0 | 0 | None | 0 | 0 | 6.31641E-06 | 0 | 0 |
| T/K | rs758799742 |
None | 0.782 | N | 0.585 | 0.242 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| T/K | rs758799742 |
None | 0.782 | N | 0.585 | 0.242 | None | gnomAD-4.0.0 | 6.56771E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1012 | likely_benign | 0.0971 | benign | -0.733 | Destabilizing | 0.003 | N | 0.195 | neutral | N | 0.509529631 | None | None | N |
| T/C | 0.3952 | ambiguous | 0.3814 | ambiguous | -0.745 | Destabilizing | 0.973 | D | 0.619 | neutral | None | None | None | None | N |
| T/D | 0.2957 | likely_benign | 0.3145 | benign | -1.55 | Destabilizing | 0.826 | D | 0.591 | neutral | None | None | None | None | N |
| T/E | 0.2492 | likely_benign | 0.2623 | benign | -1.514 | Destabilizing | 0.575 | D | 0.579 | neutral | None | None | None | None | N |
| T/F | 0.2373 | likely_benign | 0.2388 | benign | -0.943 | Destabilizing | 0.826 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/G | 0.2746 | likely_benign | 0.2865 | benign | -0.997 | Destabilizing | 0.404 | N | 0.657 | neutral | None | None | None | None | N |
| T/H | 0.2046 | likely_benign | 0.2017 | benign | -1.406 | Destabilizing | 0.022 | N | 0.513 | neutral | None | None | None | None | N |
| T/I | 0.1252 | likely_benign | 0.1223 | benign | -0.112 | Destabilizing | 0.007 | N | 0.321 | neutral | N | 0.508618272 | None | None | N |
| T/K | 0.1503 | likely_benign | 0.1442 | benign | -0.79 | Destabilizing | 0.782 | D | 0.585 | neutral | N | 0.509160275 | None | None | N |
| T/L | 0.1144 | likely_benign | 0.1188 | benign | -0.112 | Destabilizing | 0.189 | N | 0.519 | neutral | None | None | None | None | N |
| T/M | 0.1113 | likely_benign | 0.1015 | benign | 0.249 | Stabilizing | 0.947 | D | 0.627 | neutral | None | None | None | None | N |
| T/N | 0.1079 | likely_benign | 0.109 | benign | -1.097 | Destabilizing | 0.826 | D | 0.476 | neutral | None | None | None | None | N |
| T/P | 0.5178 | ambiguous | 0.5977 | pathogenic | -0.288 | Destabilizing | 0.782 | D | 0.637 | neutral | D | 0.648369659 | None | None | N |
| T/Q | 0.2127 | likely_benign | 0.2021 | benign | -1.311 | Destabilizing | 0.906 | D | 0.644 | neutral | None | None | None | None | N |
| T/R | 0.1173 | likely_benign | 0.1123 | benign | -0.553 | Destabilizing | 0.782 | D | 0.637 | neutral | N | 0.509482545 | None | None | N |
| T/S | 0.115 | likely_benign | 0.1162 | benign | -1.162 | Destabilizing | 0.338 | N | 0.441 | neutral | N | 0.508640785 | None | None | N |
| T/V | 0.1331 | likely_benign | 0.129 | benign | -0.288 | Destabilizing | 0.088 | N | 0.43 | neutral | None | None | None | None | N |
| T/W | 0.5944 | likely_pathogenic | 0.5816 | pathogenic | -1.002 | Destabilizing | 0.991 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/Y | 0.2535 | likely_benign | 0.2433 | benign | -0.653 | Destabilizing | 0.826 | D | 0.712 | prob.delet. | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.